title: Collaborative regulation of development but independent control of metabolism by two epidermis-specific transcription factors in Caenorhabditis elegans.
abstract: Cell fate specification is typically initiated by a master regulator, which is relayed by tissue-specific regulatory proteins (usually transcription factors) for further enforcement of cell identities, but how the factors are coordinated among each other to "finish up" the specification remains poorly understood. Caenorhabditis elegans epidermis specification is initiated by a master regulator, ELT-1, that activates its targets, NHR-25 and ELT-3, two epidermis-specific transcription factors that are important for development but not for initial specification of epidermis, thus providing a unique paradigm for illustrating how the tissue-specific regulatory proteins work together to enforce cell fate specification. Here we addressed the question through contrasting genome-wide in vivo binding targets between NHR-25 and ELT-3. We demonstrate that the two factors bind discrete but conserved DNA motifs, most of which remain in proximity, suggesting formation of a complex between the two. In agreement with this, gene ontology analysis of putative target genes suggested differential regulation of metabolism but coordinated control of epidermal development between the two factors, which is supported by quantitative analysis of expression of their specific or common targets in the presence or absence of either protein. Functional validation of a subset of the target genes showed both activating and inhibitory roles of NHR-25 and ELT-3 in regulating their targets. We further demonstrated differential control of specification of AB and C lineage-derived epidermis. The results allow us to assemble a comprehensive gene network underlying C. elegans epidermis development that is likely to be widely used across species and provides insights into how tissue-specific transcription factors coordinate with one another to enforce cell fate specification initiated by its master regulator.
authors.affiliation: From the Department of Biology, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Jiaofang
authors.initials: J
authors.lastname: Shao
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Wing Sze
authors.initials: WS
authors.lastname: Ho
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Ren
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: An
authors.forename: Ming Kin
authors.initials: MK
authors.lastname: Wong
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.forename: Dongying
authors.initials: D
authors.lastname: Xie
authors.forename: John
authors.initials: J
authors.lastname: Stamatoyannopoulos
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055106:Genome-Wide Association Study; D009928:Organ Specificity / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C096869:ELT-1 protein, C elegans; D050980:GATA Transcription Factors; D014157:Transcription Factors; C118721:elt-3 protein, C elegans; C486359:nuclear hormone receptor NHR-25, C elegans
keywords: C. elegans; Cell Differentiation; Chromatin Immunoprecipitation (ChIP); Epithelium; Gene Expression; Gene Regulation